Possible association of acute lateral-wall myocardial infarction and bitter orange supplement

OBJECTIVE: To report a possible incidence of acute lateral-wall myocardial infarction (MI) coinciding with the use of a Citrus aurantium L. (bitter orange)-containing dietary supplement in a patient with undetected coronary vascular disease. CASE SUMMARY: A 55-year-old white woman presented to the emergency department with symptoms of dull aching shoulder and chest pain. A review of medications during cardiac rehabilitation revealed the patient had ingested a multicomponent dietary supplement for weight loss containing 300 mg of bitter orange (Edita's Skinny Pill) for the past year. Although the patient's past medical history did not include hypertension, coronary disease, or hyperlipidemia, an arteriogram revealed a lesion in the left main coronary artery. She did have a smoking history. She was diagnosed with acute lateral-wall MI and hospitalized for 4 days. DISCUSSION: Consumers generally consider dietary supplements safe. However, some supplements taken for weight loss contain ingredients that have been associated with cardiovascular events. Although consumers are becoming more aware of the serious adverse effects secondary to products containing ingredients such as Ma huang and ephedra, reports involving other ingredients are increasing. Bitter orange or synephrine, found in bitter orange, has been associated with adverse cardiovascular reactions. Based on the Naranjo probability scale, C. aurantium is possibly associated with this cardiovascular event. CONCLUSIONS: The use of C. aurantium-containing supplements may present as a risk for cardiovascular toxicity; however, additional studies/case reports are needed to validate this conclusion.     

Squamous cell carcinoma of the lung presenting with cutaneous leukocytoclastic vasculitis: a case report

An elderly patient with paraneoplastic cutaneous leukocytoclastic vasculitis (CLV) leading to the discovery of an as-yet asymptomatic, potentially surgically curable squamous cell carcinoma of the lung is presented. This type of vasculitis has not been previously described in association with this type of lung cancer. Since vasculitic paraneoplastic syndromes, including CLV, may develop before the clinical presentation of malignant tumors, the present case and others previously reported strongly suggest that in apparently idiopathic CLV, patients should be evaluated for the presence of occult malignancy that could be curable by early detection.     

CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain

In light of the adverse side-effects of opioids, cannabinoid receptor agonists may provide an effective alternative for the treatment of cancer pain. This study examined the potency and efficacy of synthetic CB1 and CB2 receptor agonists in a murine model of tumor pain. Intraplantar injection of the CB1 receptor agonist arachidonylcyclopropylamide (ED(50) of 18.4 μg) reduced tumor-related mechanical hyperalgesia by activation of peripheral CB1 but not CB2 receptors. Similar injection of the CB2 receptor agonist AM1241 (ED50 of 19.5 μg) reduced mechanical hyperalgesia by activation of peripheral CB2 but not CB1 receptors. Both agonists had an efficacy comparable with that of morphine (intraplantar), but their analgesic effects were independent of opioid receptors. Isobolographic analysis of the coinjection of arachidonylcyclopropylamide and AM1241 determined that the CB1 and CB2 receptor agonists interacted synergistically to reduce mechanical hyperalgesia in the tumor-bearing paw. These data extend our previous findings that the peripheral cannabinoid receptors are a promising target for the management of cancer pain and mixed cannabinoid receptor agonists may have a therapeutic advantage over selective agonists.     

Chronic administration of the antiretroviral nevirapine increases body weight, food, and water intake in albino Wistar rats

Abstract Background: Nevirapine (NVP) is an antiretroviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in the blood. This study was undertaken to investigate the effect of chronic administration of NVP on body weight, food, and water intake using apparently healthy albino Wistar rats. Methods: Twenty adult albino Wistar rats (50-125 g body weight) were used for the study. Rats in the control group (n=10) were fed normal rodent chow, whereas the NVP group (n=10) were fed by gavage NVP (0.4 mg/kg body weight) two times daily (07.00 h and 18.00 h) in addition to normal rodent chow for 12 weeks. All animals were allowed free access to clean drinking water. Results: Results showed that the mean daily food and water intake in the NVP group were significantly higher (p<0.001) when compared with the control group, respectively. The mean change in body weight in the NVP group was significantly higher (p<0.001) than the control group. Conclusions: These results suggest that chronic administration of NVP may increase body weight in rats, probably due to its stimulatory effects on food and water intake.     

Acutely calcified hematoma mimicking a displaced medial epicondyle fracture

We present an interesting and unusual case of an acutely calcified pin-site infection hematoma mimicking a displaced cartilaginous medial epicondyle, in a child with a Gartland type III fracture. The treatment of such pathology could be confusing and may interfere with the correct clinical decision-making process. To our knowledge, this is the first presentation of such a case.     

Undiagnosed sleep-related breathing disorders are associated with focal brainstem atrophy in the elderly

Background: Sleep‐related breathing disorders (SRBDs) affect as many as 40% of elderly people. The association of SRBDs with structural brain abnormalities remains unclear. In this observational study, we evaluated gray matter changes in the brain associated with sleep abnormalities in volunteers and their relationship with the severity of SRBDs. Methods: One hundred fifty two healthy subjects aged 66.0 ± 0.6 years‐old underwent tridimensional brain MRI and nocturnal polygraphic recording during which apnea/hypopnea index (AHI) and the oxyhemoglobin desaturation index (ODI) were measured. Using voxel‐based morphometry, we investigated the presence of gray matter abnormalities in association with AHI and ODI. Findings: Seventy‐six subjects (50%) had SRBDs defined by an AHI ≥ to 15 and 25 subjects (16%) SRBDs defined by an ODI ≥ 15, in the absence of systematic excessive daytime sleepiness. A significant symmetrical loss of gray matter in the intermediate reticular zone of the bulbopontine area was found to correlate with both AHI and ODI (P < 0.05 corrected for multiple comparisons for cluster significance). Interpretation: This gray matter volume decrease in brain regions involved in breathing/autonomic functions, as well as their correlation with the severity of the disorder, suggests a pathophysiological link between structural changes and SRBDs. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study

Background

Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD).

Objective

We conducted a phase I–II clinical study to assess the feasibility, long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD.

Methods

Thirteen patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1–3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT‐PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson''s Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson''s Disease Rating Scale III score in the off‐medication state. Seven patients had ¹⁸F‐dopa positron emission tomography scans before and 1 year after transplantation.

Results

Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6–12 months after transplantation (5–74%). Overall, mean improvement at 6 months was 23%. In the long term (3 years), 3 of 6 patients still maintained improvement (15–48%). None of the patients developed off‐period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non‐significant 5% increase in mean putaminal ¹⁸F‐dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal ¹⁸F‐dopa uptake (r = −0.829; p = 0.042).

Conclusions

CB autotransplantation may induce clinical effects in patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.Parkinson disease (PD) is a progressive neurodegenerative disorder of unknown aetiology. Its main pathological hallmark is the degeneration of midbrain dopaminergic neurons projecting to the striatum, although other neuronal systems are also affected.¹ Current pharmacological and surgical therapies are symptomatically effective but their long term utility is limited because of disease progression.^2,3 Therefore, there is a need for neuroprotective and/or neurorestorative therapies capable of arresting or reversing the neurodegenerative process.Over the past two decades, cell replacement therapies have been tested in PD patients with the objective of restoring the striatal dopaminergic deficit.⁴ Transplantation of fetal mesencephalic neurons, the most frequently used technique, can increase the striatal dopamine storage, but does not always produce the expected clinical benefit and may induce disabling off‐medication dyskinesias.^5,6 Thus it appears that the ectopic placement of dopamine secreting cells in the striatum is not the ideal approach to compensate for progressive nigrostriatal neuronal loss.⁷ Given this scenario, the clinical applicability of other transplantation procedures based on a similar rationale (eg, intrastriatal grafting of porcine mesencephalic neurons, retinal pigment epithelial cells or stem cell derived dopaminergic neurons) is, for the moment, uncertain.More recently, other strategies aiming to protect or restore the nigrostriatal pathway have emerged. Glial cell line derived neurotrophic factor (GDNF) has been shown to exert neuroprotective and neurorestorative actions in animal models of PD.^8,9,10 The clinical efficacy of GDNF has been assayed in clinical trials, but the method of delivery is a critical issue. Whereas intraventricular administration failed to induce clinical benefit,¹¹ intraputaminal infusion showed promising results,^12,13 although a placebo controlled trial using this route has been halted because of lack of efficacy and safety concerns about recombinant human GDNF administration.¹⁴ Other alternative methods being tested experimentally in parkinsonian animals include in vivo gene therapy using GDNF encoding viral vectors^15,16,17 and the intrastriatal grafting of recombinant GDNF producing cell lines.^18,19,20,21 Carotid body (CB) glomus cells are neural crest derived dopaminergic cells that express high levels of GDNF. Glomus cell GDNF production is resistant to 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine administration, and maintained in aged rodents or after intrastriatal grafting.^22,23 The survival rate of these cells after transplantation (>70%) is particularly high as hypoxia stimulates their growth and function. Moreover, CB grafts performed in young rats remain active for the entire animal lifespan.^22,23 Transplantation of CB cell aggregates has been shown to induce a neurotrophic mediated recovery in animal models of PD^{22,23,24,25,26,27} and stroke.^28,29We conducted a phase I–II video blinded clinical study to assess the long term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with advanced PD. In a pilot report of our first six patients, we showed this procedure to be feasible.³⁰ Here we report the clinical outcomes and prognostic factors in the whole study (n = 13), as well as ¹⁸F‐dopa positron emission tomography (PET) outcomes in a subgroup of patients (n = 7).     

Evaluation of expiratory volume, diffusion capacity, and exercise tolerance following major lung resection: a prospective follow-up analysis

BACKGROUND: Lung resections determine a variable functional reduction depending on the extent of the resection and the time elapsed from the operation. The objectives of this study were to prospectively investigate the postoperative changes in FEV(1), carbon monoxide lung diffusion capacity (Dlco), and exercise tolerance after major lung resection at repeated evaluation times. METHODS: FEV(1), Dlco, and peak oxygen consumption (Vo(2)peak) calculated using the stair climbing test were measured in 200 patients preoperatively, at discharge, and 1 month and 3 months after lobectomy or pneumonectomy. Preoperative and repeated postoperative measures were compared, and a time-series, cross-sectional regression analysis was performed to identify factors associated with postoperative Vo(2)peak. RESULTS: One month after lobectomy, FEV(1), Dlco, and Vo(2)peak values were 79.5%, 81.5%, and 96% of preoperative values and recovered up to 84%, 88.5%, and 97% after 3 months, respectively. One month after pneumonectomy, FEV(1) percentage of predicted, Dlco percentage of predicted, and Vo(2)peak values were 65%, 75%, and 87% of preoperative values, and were 66%, 80%, and 89% after 3 months, respectively. Three months after lobectomy, 27% of patients with COPD had improved FEV(1), 34% had improved Dlco, and 43% had improved Vo(2)peak compared to preoperative values. The time-series, cross-sectional regression analysis showed that postoperative Vo(2)peak values were directly associated with preoperative values of Vo(2)peak, and postoperative values of FEV(1) and Dlco, and were inversely associated with age and body mass index. CONCLUSIONS: Our findings may be used during preoperative counseling and for deciding eligibility for operation along with other more traditional measures of outcome.